Department of Neurobiology, Care Sciences and Society, Division of Neurodegeneration, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
Prog Neurobiol. 2010 Feb 9;90(2):256-62. doi: 10.1016/j.pneurobio.2009.10.015. Epub 2009 Oct 21.
Cells in the nervous system can respond to different kinds of stress, e.g. injury, with production and release of inflammatory molecules, including cytokines. One of the most important proinflammatory cytokines is interleukin-1, affecting most organs of the body. The high constitutive expression of interleukin-1 in the adrenal gland provides a source for local and systemic actions, in addition to activated monocytes. In the brain, the constitutive expression is low, but activated microglia produce and release interleukin-1 during pathological conditions such as neurodegenerative disorders (e.g. stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease). Interleukin-1 has an important role in mediating 'sickness symptoms' such as fever, in response to infections. Its role in neurodegeneration is not fully elucidated, but there is evidence for involvement in both amyloidosis and tau pathology, major neuropathological hallmarks of Alzheimer's disease. The interleukin-1 family at present consists of 11 members, one of which is the endogenous receptor antagonist. Overexpression of this antagonist in the CNS in a transgenic mouse strain, Tg hsIL-1ra, has allowed studies on morphological and functional effects of blocking interleukin-1 receptor-mediated activity in the brain. Marked alterations of brain morphology such as reduced hippocampal and cortical volume correlate with behavioural deficits. Decreased anxiety and impaired long-term memory are among the consequences. Intact interleukin-1 signalling is important for the brain's ability to adapt to acute and chronic neuroinflammation. Increased amplitude and prolongation of proinflammatory cytokine production underly the behavioural alterations characteristic for ageing. Moreover, deregulated expression of interleukin-1 is associated with ageing-related chronic neurodegenerative disorders.
神经系统中的细胞可以对不同类型的应激（例如损伤）做出反应，产生和释放炎症分子，包括细胞因子。其中最重要的促炎细胞因子之一是白细胞介素-1，它影响身体的大多数器官。肾上腺中白细胞介素-1的高组成型表达提供了局部和全身作用的来源，除了激活的单核细胞之外。在大脑中，组成型表达水平较低，但在神经退行性疾病（例如中风、创伤性脑损伤、阿尔茨海默病、帕金森病）等病理条件下，激活的小胶质细胞会产生和释放白细胞介素-1。白细胞介素-1在介导“疾病症状”（如感染后的发热）方面起着重要作用。它在神经退行性变中的作用尚未完全阐明，但有证据表明它参与了淀粉样蛋白和 tau 病理学，这是阿尔茨海默病的主要神经病理学特征。白细胞介素-1家族目前由 11 个成员组成，其中一个是内源性受体拮抗剂。在一种转基因小鼠品系 Tg hsIL-1ra 中，在中枢神经系统中过度表达这种拮抗剂，使得能够研究阻断白细胞介素-1受体介导的活性对大脑的形态和功能影响。显著的脑形态改变，如海马和皮质体积减少，与行为缺陷相关。焦虑减少和长期记忆受损是其中的后果之一。完整的白细胞介素-1信号对于大脑适应急性和慢性神经炎症的能力很重要。促炎细胞因子产生的幅度增加和持续时间延长是与衰老相关的行为改变的基础。此外，白细胞介素-1的失调表达与与年龄相关的慢性神经退行性疾病有关。
